Bioorganic and Medicinal Chemistry p. 3248 - 3259 (2015)
Update date:2022-08-17
Topics:
Abdelazeem, Ahmed H.
Khan, Shabana I.
White, Stephen W.
Sufka, Kenneth J.
McCurdy, Christopher R.
Abstract Benzoxazolone and benzothiazolone were used as template blocks to develop two series of dimers as anti-inflammatory and analgesic agents based on the concept of bivalent ligands. The first series (I) involved varying the carbon chain lengths extending from the piperazine core to the nitrogen atom of the dibenzo[d]oxazol-2(3H)-one or dibenzo[d]thiazol-2(3H)-one. The second series (II) was designed by changing the attachment point. All compounds were screened for their in vitro anti-inflammatory activity in terms of the inhibition of inducible nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-κB). Seventeen compounds inhibited both targets. Eleven of them exhibited IC50 values below 3 μM while five compounds showed IC50 values of 1 μM or below. Most of the compounds were found to be devoid of cytotoxicity against mammalian kidney and solid tumors cell lines up to 25 μg/mL. In vivo anti-inflammatory and antinociceptive studies revealed that compounds 3j, 5t and 8b have significant anti-inflammatory and analgesic activity comparable to that of indomethacin and ketorolac, respectively.
View MoreShanDong XinDa Chemical CO.,LTD
Contact:086-0311-87580543
Address:No.168, High Technology Development Zone Jinan Shandong China
Daicel Chiral Technologies (China)CO.,LTD
Contact:021-5046-0086*8
Address:Part C, FL 5, the 16th Building, No. 69, XiYa Road, WaiGaoQiao Free Trade Zone, Shanghai, 200131, P.R.China
Landz International Company Ltd.
Contact:0086-21-58891610
Address:985 Dongfang Road, Pudong, Shanghai 200122 China
Contact:+86-21-38122007
Address:2, Lane 1123, Kangqiao Road, Pudong New Area, Shanghai
JIANGXI ZHANGFENG CHEMICAL CO., LTD.
Contact:+86-0799-3413066
Address:Xiyuan village, Xiabu Town, Xiangdong District
Doi:10.1002/cbic.201800248
(2019)Doi:10.1021/jm501772w
(2015)Doi:10.1016/j.cclet.2014.09.020
(2015)Doi:10.1021/acs.jmedchem.8b01733
(2019)Doi:10.1039/QJ8500200052
(1850)Doi:10.1002/hlca.19810640322
(1981)